Aims. The success of anterior cruciate ligament reconstruction (ACLR)
depends on osseointegration at the graft-tunnel interface and intra-articular
ligamentization. Our aim was to conduct a systematic review of clinical
and preclinical studies that evaluated biological augmentation of
graft healing in ACLR. . Materials and Methods. In all, 1879 studies were identified across three databases.
Following assessment against strict criteria, 112 studies were included
(20 clinical studies; 92 animal studies). . Results. Seven categories of biological interventions were identified:
growth factors, biomaterials, stem cells, gene therapy, autologous
tissue, biophysical/environmental, and pharmaceuticals. The methodological
quality of animal studies was moderate in 97%, but only 10% used
clinically relevant outcome measures. The most interventions in
clinical trials target the graft-tunnel interface and are applied
intraoperatively. Platelet-rich plasma is the most studied intervention,
but the clinical outcomes are mixed, and the methodological quality
of studies was suboptimal. Other biological therapies investigated
in clinical trials include: remnant-augmented ACLR; bone substitutes;
calcium phosphate-hybridized grafts; extracorporeal
